IBR   13079
INSTITUTO DE BIOLOGIA MOLECULAR Y CELULAR DE ROSARIO
Unidad Ejecutora - UE
artículos
Título:
Novel cytostatic activity of the trypanocidal drug Benznidazole
Autor/es:
PASCUTTI MARÍA FERNANDA; CAMPODONICO GERARDO; GARCÍA FABIANA; MANARIN ROMINA; BOTTASSO OSCAR; REVELLI SILVIA.; SERRA ESTEBAN
Revista:
INTERNATIONAL IMMUNOPHARMACOLOGY
Referencias:
Año: 2009 vol. 9 p. 739 - 745
ISSN:
1567-5769
Resumen:
We have shown that Benznidazole (BZL), a compound with well documented trypanocidalactivity, possesses anti-inflammatory properties and inhibits the nuclear factor κB (NF-κB).Given the relationship between this transcription factor and cell growth, in this study we addressthe role of NF-κB blockade by BZL in the proliferation of different cell lines. Our studiesdemonstrate that this compound significantly reduced proliferation of RAW 264.7 macrophagecell line, as assessed by trypan blue exclusion, MTT reduction and [3H]-thymidine incorporation,at a concentration shown to inhibit NF-κB. Treatment with BZL also led to growth arrest in CHO,MDCK and HeLa cells. Interestingly, growth inhibition was found to be a reversible process, notaccompanied by significant cell death, indicating that the drug behaves mainly as a cytostaticcompound. As this effect might be related to NF-κB inhibition, we next evaluated whether otherNF-κB inhibitors could induce growth arrest in RAW 264.7 and HeLa cells. We found that IKKinhibition led to growth arrest in both cell lines, indicating that NF-κB inhibition may be thepotential mechanism by which BZL inhibits cell proliferation. To the best of our knowledge, this isthe first report of an anti-proliferative activity of the trypanocidal drug against different cell linesand provides a mechanistic insight that may help understand some of the adverse effectsassociated with prolonged treatment.KEYWORDS: Benznidazole; proliferation; NF-κB; adverse effects